Mycobiology

The Korean Society of Mycology (한국균학회)
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LAMMER Kinase Modulates Cell Cycle by Phosphorylating the MBF Repressor, Yox1, in Schizosaccharomyces pombe

  • Kibum Park (Laboratory of Cellular Differentiation, Department of Microbiology and Molecular Biology, College of Bioscience and Biotechnology, Chungnam National University) ;
  • Joo-Yeon Lim (Department of Microbiology and Immunology, Indiana University School of Medicine-Terre Haute) ;
  • Je-Hoon Kim (Laboratory of Cellular Differentiation, Department of Microbiology and Molecular Biology, College of Bioscience and Biotechnology, Chungnam National University) ;
  • Jieun Lee (Laboratory of Cellular Differentiation, Department of Microbiology and Molecular Biology, College of Bioscience and Biotechnology, Chungnam National University) ;
  • Songju Shin (Laboratory of Cellular Differentiation, Department of Microbiology and Molecular Biology, College of Bioscience and Biotechnology, Chungnam National University) ;
  • Hee-Moon Park (Laboratory of Cellular Differentiation, Department of Microbiology and Molecular Biology, College of Bioscience and Biotechnology, Chungnam National University)
  • Received : 2023.07.23
  • Accepted : 2023.09.11
  • Published : 2023.10.31
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Abstract

Lkh1, a LAMMER kinase homolog in the fission yeast Schizosaccharomyces pombe, acts as a negative regulator of filamentous growth and flocculation. It is also involved in the response to oxidative stress. The lkh1-deletion mutant displays slower cell growth, shorter cell size, and abnormal DNA content compared to the wild type. These phenotypes suggest that Lkh1 controls cell size and cell cycle progression. When we performed microarray analysis using the lkh1-deletion mutant, we found that only four of the up-regulated genes in the lkh1-deletion were associated with the cell cycle. Interestingly, all of these genes are regulated by the Mlu1 cell cycle box binding factor (MBF), which is a transcription complex responsible for regulating the expression of cell cycle genes during the G1/S phase. Transcription analyses of the MBF-dependent cell-cycle genes, including negative feedback regulators, confirmed the up-regulation of these genes by the deletion of lkh1. Pull-down assay confirmed the interaction between Lkh1 and Yox1, which is a negative feedback regulator of MBF. This result supports the involvement of LAMMER kinase in cell cycle regulation by modulating MBF activity. In vitro kinase assay and NetPhosK 2.0 analysis with the Yox1T40,41A mutant allele revealed that T40 and T41 residues are the phosphorylation sites mediated by Lkh1. These sites affect the G1/S cell cycle progression of fission yeast by modulating the activity of the MBF complex.

Keywords

Acknowledgement

This work was funded by the grants from the National Research Foundation of Korea, grant number 2015025545 and 2021R1A2C1009229 (to HMP)

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